We propose to create a system for highly selective transcranial tissue ablation and coagulation by combining the techniques of time reversal (TR) acoustics and acoustic droplet vaporization (ADV). The project is subdivided into an R21 phase, where we create the necessary fundamental apparatus and techniques and an R33 phase where we apply the apparatus and techniques to eventually perform in vivo, transcranial tissue ablation with a sharply focused ultrasound beam. The crucial hardware component in the R21 phase is an efficient chaotic reverberant cavity (CRC) that approaches the capabilities of a full, 2D array, at a much reduced cost and with less complexity and fragility. It will be driven by a TR-system operating with point beacons to overcome any aberrators between the CRC and the beacon. Acoustically vaporized droplets will yield approximately 30-60 micron diameter gas bubbles that will be used as point beacons for refocusing. Development of a library of focused beams for the CRC will allow us to scan and image in an unknown/unaberrated 3D space. In the R33 phase of this project, we will extend the CRC's frequency range to include 100 kHz to 5 MHz. This will allow us to drive bubbles in a nonlinear manner and enhance bubble detection and scattering. Moreover, higher frequencies will allow for easier vaporization but are more subject for higher insertion loss and attenuation of incident waves. Possibly, higher frequencies will also result in better spatial resolution after aberration correction. Phantoms with spatially distributed droplets/gas bubbles will be used to demonstrate an iterative focusing technique to identify and utilize multiple beacons individually. From this ability we will then analyze the system's capability to perform dynamic focusing (both with regard to location and focal zone shape). Finally, the system will be analyzed for its (aberration correction) performance through an ex vivo human skull cap in conjunction with 1) a tissue mimicking US phantom, 2) ex vivo rabbit brain, and 3) in vivo rabbit brain with the rabbit's skull cap removed. The pressure threshold for the onset of lesions will be determined after aberration correction. Upon positive outcome of the in vivo section we will design a clinical study for in human application of this methodology. [unreadable] [unreadable] [unreadable]